Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water‐soluble fullerene‐polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular stomatitis virus coat glycoprotein (VSV‐G) with baby hamster kidney cells serving as a model of host cell. Interference with L‐selectin‐ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)‐based inhibition assay and the leukocyte cell (NALM‐6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico‐ to nanomolar half maximal inhibitory concentrations (IC50) are achieved. With their highly antiviral and anti‐inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications.